Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study

Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy...

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Published inHepatology (Baltimore, Md.) Vol. 50; no. 4; pp. 1113 - 1120
Main Authors Carter‐Kent, Christine, Yerian, Lisa M., Brunt, Elizabeth M., Angulo, Paul, Kohli, Rohit, Ling, Simon C., Xanthakos, Stavra A., Whitington, Peter F., Charatcharoenwitthaya, Phunchai, Yap, Jason, Lopez, Rocio, McCullough, Arthur J., Feldstein, Ariel E.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2009
Wiley
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Abstract Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy‐proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin‐eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7‐point scale. The median age was 12 years (range, 4‐18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS ≥5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). Conclusion: Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. (HEPATOLOGY 2009.)
AbstractList Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS > or =5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease.
Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores ( P < 0.01), perisinusoidal fibrosis ( P < 0.001), and NAS ≥5 ( P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis ( P = 0.003).
UNLABELLEDNonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well-characterized, biopsy-proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin-eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7-point scale. The median age was 12 years (range, 4-18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS > or =5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). CONCLUSIONOur results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease.
Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum and significance of histological lesions in pediatric patients. We conducted a multicenter study of children with well‐characterized, biopsy‐proven NAFLD to (1) assess the presence and significance of a constellation of histological lesions and (2) identify clinical and laboratory predictors of disease severity. One hundred thirty children with NAFLD seen from 1995 to 2007 in five centers in the United States and Canada were studied. Clinical and laboratory data were collected. Slides stained with hematoxylin‐eosin and trichrome were evaluated by two liver pathologists. The NAFLD activity score (NAS) and the pattern of liver injury (type 1 or adult versus type 2 or pediatric nonalcoholic steatohepatitis [NASH]) were recorded. Fibrosis was staged using a published 7‐point scale. The median age was 12 years (range, 4‐18 years); 63% were boys, and 52% were Caucasian. Fibrosis was present in 87% of patients; of these, stage 3 (bridging fibrosis) was present in 20%. No patient had cirrhosis. The median NAS was 4. Overlapping features of both type 1 (adult pattern) and type 2 (pediatric pattern) NASH were found in 82% of patients. Compared with patients with no or mild fibrosis, those with significant fibrosis were more likely to have higher lobular and portal inflammation scores (P < 0.01), perisinusoidal fibrosis (P < 0.001), and NAS ≥5 (P < 0.005). Serum aspartate aminotransferase levels were the only clinical or laboratory data that independently predicted severity of fibrosis (P = 0.003). Conclusion: Our results highlight the limitations of published proposals to classify pediatric NAFLD, and identified histological lesions associated with progressive disease. (HEPATOLOGY 2009.)
Author Charatcharoenwitthaya, Phunchai
Xanthakos, Stavra A.
Whitington, Peter F.
Ling, Simon C.
Kohli, Rohit
Lopez, Rocio
Feldstein, Ariel E.
Carter‐Kent, Christine
Yerian, Lisa M.
Yap, Jason
Brunt, Elizabeth M.
Angulo, Paul
McCullough, Arthur J.
AuthorAffiliation 7 Division of Gastroenterology and Hepatology, Children's Memorial Hospital, Chicago, IL
8 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH
3 Department of Pathology and Immunology, Washington University, St. Louis, MO
9 Digestive Disease Institute, Cleveland Clinic, Cleveland, OH
4 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
2 Department of Pathology, Cleveland Clinic, Cleveland, OH
6 Division of Gastroenterology and Hepatology, The Hospital for Sick Children, Toronto, Ontario, Canada
5 Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
10 Department of Cell Biology, Cleveland Clinic, Cleveland, OH
1 Department of Pediatric Gastroenterology and Nutrition, Cleveland Clinic, Cleveland, OH
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  surname: Carter‐Kent
  fullname: Carter‐Kent, Christine
– sequence: 2
  givenname: Lisa M.
  surname: Yerian
  fullname: Yerian, Lisa M.
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  surname: Angulo
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  surname: Ling
  fullname: Ling, Simon C.
– sequence: 7
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– sequence: 8
  givenname: Peter F.
  surname: Whitington
  fullname: Whitington, Peter F.
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  givenname: Phunchai
  surname: Charatcharoenwitthaya
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  fullname: Yap, Jason
– sequence: 11
  givenname: Rocio
  surname: Lopez
  fullname: Lopez, Rocio
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  givenname: Arthur J.
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  fullname: McCullough, Arthur J.
– sequence: 13
  givenname: Ariel E.
  surname: Feldstein
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https://www.ncbi.nlm.nih.gov/pubmed/19637190$$D View this record in MEDLINE/PubMed
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    fullname: Wieckowska
– volume: 20
  start-page: S40
  issue: Suppl 1
  year: 2007
  ident: R5-18-20241124
  article-title: Pathology of fatty liver disease.
  publication-title: Mod Pathol
  doi: 10.1038/modpathol.3800680
  contributor:
    fullname: Brunt
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Snippet Nonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on the spectrum...
UNLABELLEDNonalcoholic fatty liver disease (NAFLD) may have distinct histological features in children and adults, but to date limited data are available on...
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SubjectTerms Adolescent
Aspartate Aminotransferases - blood
Biological and medical sciences
Biopsy
Canada
Child
Child, Preschool
Cohort Studies
Disease Progression
Fatty Liver - blood
Fatty Liver - diagnosis
Fatty Liver - pathology
Female
Gastroenterology. Liver. Pancreas. Abdomen
Humans
Liver - pathology
Liver Cirrhosis - pathology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Male
Medical sciences
Predictive Value of Tests
Prognosis
Retrospective Studies
Severity of Illness Index
United States
Title Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fhep.23133
https://www.ncbi.nlm.nih.gov/pubmed/19637190
https://search.proquest.com/docview/67678918
https://pubmed.ncbi.nlm.nih.gov/PMC2775705
Volume 50
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